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Biomedical subjects

J Klastersky

Publications and source records attributed to J Klastersky.

At least 163 records · Page 9Linked to original sources
PubMed1987

Bactericidal activity and killing rate of serum in volunteers receiving teicoplanin alone or in combination with oral or intravenous rifampin.

A total of 10 volunteers, in two groups of 5 each, received the following on separate days: group 1,200 mg of teicoplanin intravenously (i.v.), 600 mg of rifampin orally, or teicoplanin-rifampin; group 2,400 mg of teicoplanin i.v., 300 mg of rifampin i.v. in 60 min, or teicoplanin-rifampin. Blood samples were obtained before, at the end, and at 1 and 6 h after the administration of the antibiotics. Bactericidal activity in serum (SBA) was measured in microtiter plates against 20 clinical isolates (five strains each) of oxacillin-susceptible and-resistant Staphylococcus aureus and Staphylococcus epidermidis. The endpoint of the SBA corresponded to 99.9% killing. Killing rates were measured in serum obtained at 1 and 6 h. The concentrations of each antibiotic were measured by bioassay. The antibiotic concentrations in serum obtained at the peak and at 1 and 6 h after the end of administration were as follows: group 1, teicoplanin, 26, 15.6, and 8.4 mg/liter; rifampin, not determined, 8.3, and 3.8 mg/liter; group 2, teicoplanin, 66, 29.4, and 11.5 mg/liter; rifampin, 14.8, 3.8, and 1.2 mg/liter. Higher median SBAs were obtained after treatment with rifampin than after that with teicoplanin. No interaction was observed between rifampin and teicoplanin. This was confirmed by determination of the killing rate in serum. Teicoplanin killed more slowly than rifampin. The combination had the same killing rate as rifampin alone. Rifampin neither improved nor antagonized the bactericidal activity of teicoplanin, as determined by the SBAs or the rate of killing.

Administration, Oral↗
PubMed1987

Serum bactericidal activity and postantibiotic effect in serum of patients with urinary tract infection receiving high-dose amikacin.

Ten patients received a 30-min infusion of amikacin (30 mg/kg) on day 1 and 15 mg/kg on day 2. Mean serum creatinine was 1.1 +/- 0.3 (standard deviation) mg/dl before and 1.0 +/- 0.3 mg/dl 3 days after the second infusion. Mean serum amikacin concentrations before, at the end of infusion, and 1, 6, 12, and 24 h after 30 and 15 mg/kg were 0, 157, 79, 31, 16, 5, 5, 85, 51, 19, 12, and 5 mg/liter, respectively. Five strains each of Staphylococcus aureus, Staphylococcus epidermidis susceptible and resistant to oxacillin, Streptococcus (Enterococcus) faecalis, corynebacterium sp. strain JK, Listeria monocytogenes, Mycobacterium fortuitum (three strains), Klebsiella pneumoniae, Serratia marcescens, Acinetobacter calcoaceticus, and Pseudomonas aeruginosa were tested. Serum bactericidal activities (SBAs) were greater than or equal to 1:8 in greater than or equal to 80% of the sera 1 and 6 h after 30 mg/kg and in greater than or equal to 60% of the sera 1 and 6 h after 15 mg/kg against Staphylococcus aureus and Staphylococcus epidermidis susceptible to oxacillin, A. calcoaceticus, and K. pneumoniae. L. monocytogenes, Serratia marcescens, and P. aeruginosa had lower SBAs. Very low or no activity was observed against oxacillin-resistant staphylococci and Streptococcus faecalis. The study of the killing rate in serum confirmed these results. Postantibiotic effect was studied by incubating a strain from each species in serum samples obtained 1 and 6 h after both regimens for 0.5, 1, or 2 h. The duration of postantibiotic effect depended on the duration of contact and the concentration of amikacin for the following organisms: oxacillin-susceptible staphylococci, L. monocytogenes, P. aeruginosa, A. calcoaceticus, K. pneumoniae, and Serratia marcescens. M. fortuitum was killed after 30 min of contact. No postantibiotic effect was observed with Streptococcus faecalis, Corynebacterium sp. strain JK, or oxacillin-resistant staphylococci. Amikacin at 30 mg/kg provided high levels and SBAs against susceptible pathogens. Prolonged postantibiotic effects were observed. No signs of nephrotoxicity occurred.

Acinetobacter↗
PubMed1987

Serum bactericidal activity against Klebsiella pneumoniae in volunteers receiving increasing doses of tobramycin with or without cefamandole.

Ten volunteers received intravenously in a randomly allocated order and on separate days the following regimens: cefamandole (15 mg/kg); tobramycin (1.5 mg/kg); tobramycin (3 mg/kg); cefamandole (15 mg/kg) + tobramycin (1.5 mg/kg); cefamandole (15 mg/kg) + tobramycin (3 mg-kg). Tobramycin serum levels were 3.7 +/- 0.7 micrograms/ml one hour after infusion of the 1.5-mg/kg and 7.8 +/- 1.6 micrograms/ml after the higher dose. Cefamandole serum levels were 26.0 +/- 5.2 micrograms/ml at the same time. Serum bactericidal activity and killing-rate studies were performed on a collection of 18 strains of Klebsiella pneumoniae. Against cefamandole-sensitive strains, all regimens were satisfactory (median serum bactericidal activity 1:16 to 1:64). Tobramycin (3 mg/kg) and both combinations were slightly more active on cefamandole-resistant strains (1:16 to 1:32) than cefamandole (1:2) and tobramycin low dose (1:8). Except for cefamandole alone, all regimens were equivalent in killing studies.

Adult↗
PubMed1987

[Basophil leukemia, development of a chronic myeloid leukemia. Apropos of a case and review of the literature].

Basophilic leukemia is a rare disease accounting for less than 2% of all hematopoietic malignancies and little is known about the best therapeutical approach. We report a case of basophilic leukemia occurring as an accelerated phase of chronic myelogenic leukemia in a 50 year old man with a past history of uranium and thorium exposure. He was successfully treated with intensive chemotherapy and total body irradiation followed by autologous peripheral stem cell transplantation. Such an approach has never been reported in this disease. However, the benefit on survival could not be evaluated because of a fatal opportunistic infection. The cases of basophilic leukemia reported in the literature are discussed.

Basophils↗
PubMed1987

Comparative in vitro activity of CI934, a new fluoroquinolone, alone and in combination with coumermycin, against gram-positive bacteria.

The in vitro activity of Cl934, a new quinolone antimicrobial agent, was studied against 314 strains of Gram-positive bacteria representing 6 genera: Staphylococcus aureus, Streptococcus faecalis, S. agalactiae, S. pyogenes, S. pneumoniae, S. milleri, viridans streptococci, Listeria monocytogenes, Corynebacterium JK, Mycobacterium fortuitum and Bacillus spp.; and compared with that of enoxacin, ciprofloxacin, penicillin G, ampicillin, coumermycin, oxacillin, vancomycin, teicoplanin, rifampin, rifapentine, LM 427, erythromycin, minocycline, tetracycline and clindamycin. The agar dilution method was used. Cl934 was very active in vitro, with MIC90 less than or equal to 0.5 mg/l against most species tested, except for S. faecalis and M. fortuitum. It was usually 2 to 8-fold more active than ciprofloxacin. Cl934 was also tested by the killing curve method, alone and in combination with coumermycin. It was rapidly bactericidal against most species tested, including S. faecalis. A synergistic interaction was observed with coumermycin against S. aureus, S. agalactiae, S. milleri and S. faecalis. The only antagonistic interaction occurred against L. monocytogenes exposed to 8 X MIC of Cl934 with 2 X MIC of coumermycin.

Aminocoumarins↗
PubMed1986

Comparative review of combination therapy: two beta-lactams versus beta-lactam plus aminoglycoside.

Febrile neutropenic patients are usually treated with a combination of a beta-lactam and an aminoglycoside. Since Pseudomonas aeruginosa is an important pathogen in these patients, the empiric use of possibly synergistic combinations against that organism has been traditionally recommended. The recent appearance of beta-lactams more active against P. aeruginosa and the well-known nephrotoxicity of aminoglycosides have led some to advocate the use of beta-lactam combinations for empiric treatment of fever in neutropenic cancer patients. This article reviews the available literature on the controlled use of combinations of beta-lactams in the treatment of febrile neutropenic patients as compared with that of combinations of beta-lactams and aminoglycosides. The review includes comparison of overall response, response in patients with septicemia or other infections, response associated with different pathogens, the effect of profound neutropenia, and an evaluation of the toxicities encountered. Overall, these results show that response rates with a combination of two beta-lactams are similar to those obtained with the combinations of a beta-lactam and an aminoglycoside for infections in patients with serious underlying disease and compromised mechanisms of defense. They also suggest that the steady emergence of resistance of pathogens to beta-lactams has often been overcome by the use of newer drugs in regard to infections caused by the Enterobacteriaceae but much less effectively in regard to P. aeruginosa. There are still important theoretic reasons for preferring an aminoglycoside-containing combination as empiric therapy in febrile neutropenic patients, and our overall conclusion is that it would be appropriate to conduct a large-scale trial comparing beta-lactam combinations with the traditional beta-lactam plus aminoglycoside regimens in that setting.

Aminoglycosides↗
PubMed1986

Concept of empiric therapy with antibiotic combinations. Indications and limits.

It appears that the use of antibiotic combinations, especially synergistic ones, is indicated for the management of gram-negative bacillary sepsis in granulocytopenic patients. Synergism is a valuable factor in increasing the serum bactericidal activity, which is highly likely to be important for a favorable outcome in these infections. The potential side effects of antimicrobial combinations should not deter clinicians from their use. The most frequently used combinations for gram-negative bacillary infections are those involving beta-lactams and aminoglycosides. Other potentially synergistic combinations exist as well; however, the clinical experience with these combinations is limited, and, as with double beta-lactam combinations, their potential for antagonism necessitates care when using them. Besides gram-negative bacillary sepsis in granulocytopenic patients, severe staphylococcal infections might represent an indication for the use of combination therapy, especially in patients with compromised mechanisms of defense against infection.

Agranulocytosis↗
PubMed1986

Empiric antimicrobial therapy with aztreonam or ceftazidime in gram-negative septicemia.

In an open, comparative study, 225 patients with severe underlying diseases and suspected gram-negative bacillary septicemia were randomly assigned to receive aztreonam or ceftazidime empirically, 2 g intravenously three times daily. Twenty-five patients in the aztreonam group and 22 in the ceftazidime group had blood cultures that grew aerobic gram-negative bacilli and were evaluable for response to therapy. All pathogenic strains were sensitive to treatment. In the aztreonam group, 22 (88 percent) patients had cures, three (12 percent) had failures, and seven (28 percent) had development of superinfections (five were caused by gram-positive cocci and two by fungi). In the ceftazidime group, 18 (82 percent) patients had cures, one had improvement, three (14 percent) had failures, and three had superinfections. The median peak serum bactericidal activity was 1:2,048 after aztreonam administration and 1:512 after ceftazidime administration. Failures were not related to resistant strains or to low serum bactericidal activity.

Adult↗
PubMed1986

[Polychemotherapy of undifferentiated small cell bronchial cancer. Long-term results].

Long-term results of 2 studies combining etoposide and adriamycin with cisplatin (CAV) or cyclophosphamide (AVE) in small cell lung cancer indicate a 2-year survival rate of 22% and 18% respectively. The complete response rate 2 years after the onset of chemotherapy was 8% (8/98) : 11% (4/36) with CAV and 5% (4/62) with AVE. Among these 8 patients, 2 had a late relapse and one died of an unrelated cause. The actual long-term survival rate was 6% with CAV and 5% with AVE.

Adult↗
PubMed1986

Effect of increasing doses of amikacin with or without piperacillin in the serum bactericidal test.

To determine whether high doses of amikacin would prevent the development of resistance in clinical isolates, the serum bactericidal activity and killing rate of conventional and high doses of amikacin and piperacillin alone and in combination were measured in volunteer sera against a series of ten strains each of Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. Amikacin serum levels were 24.9 +/- 6.0 mg/l 1 h after infusion of the 7.5 mg/kg dose and 44.8 +/- 5.0 mg/l after the two-fold dose. Median serum bactericidal titers for low dose piperacillin + amikacin were 1:8-1:64 and for high-dose piperacillin + amikacin 1:16-1:128. Both were satisfactory, except against piperacillin-resistant Pseudomonas aeruginosa (median bactericidal titers less than or equal to 1:2), and both combinations had equivalent killing rates.

Adult↗
PubMed1986

Serum bactericidal activity of mezlocillin, ceftazidime, mezlocillin/ceftazidime and mezlocillin/amikacin against Klebsiella pneumoniae and Pseudomonas aeruginosa.

Sera of volunteers receiving 1 g mezlocillin, 5 g mezlocillin, 1 g ceftazidime, 3 g ceftazidime, 1 g mezlocillin plus 1 g ceftazidime, and 1 g mezlocillin plus 500 mg amikacin, respectively, were evaluated for bactericidal activity against clinical isolates of Klebsiella pneumoniae and Pseudomonas aeruginosa. The titers of bactericidal activity against Klebsiella pneumoniae in serum from subjects receiving ceftazidime were higher than with other regimens both one and six hours after administration. Peak titers of bactericidal activity greater than or equal to 1:8 were also achieved more often against Pseudomonas aeruginosa in sera from subjects receiving ceftazidime than with other regimens. Killing studies confirmed these results. Although the checkerboard technique indicated synergism with the combination mezlocillin plus amikacin in vitro, this was not confirmed in vivo. Single drug therapy with ceftazidime was superior to the tested combinations.

Amikacin↗